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首页> 外文期刊>Oncogene >Caspase-1 activator Ipaf is a p53-inducible gene involved in apoptosis
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Caspase-1 activator Ipaf is a p53-inducible gene involved in apoptosis

机译：Caspase-1激活因子Ipaf是p53诱导的凋亡相关基因

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The tumor suppressor protein p53 regulates transcription of many genes that mediate cell cycle arrest, apoptosis, DNA repair and other cellular responses. Here we show that Ipaf, a human CED-4 homologue and an activator of caspase-1, is induced by p53. Overexpression of p53 by transfection in U2OS and A549 cells increased Ipaf mRNA levels. Treatment of p53-positive cell lines U2OS and MCF-7 with the DNA damaging drug, doxorubicin, which increases p53 protein level, induced expression of Ipaf mRNA but similar treatment of MCF-7-mp53 (a clone of MCF-7 cells expressing mutant p53) and p53-negative K562 cells showed much less induction of Ipaf gene expression. Expression analysis for Ipaf mRNA in doxorubicin-treated human tumor cell lines suggests that p53-dependent as well as p53-independent mechanisms are involved in the regulation of Ipaf gene expression in a cell-type-specific manner. The Ipaf promoter was activated by normal p53 but not by His273 mutant of p53. A functional p53-binding site was identified in the Ipaf promoter. A dominant-negative mutant of Ipaf inhibited p53-induced and doxorubicin-induced apoptosis by about 50%. Ipaf-directed small hairpin RNA downregulated p53-induced Ipaf gene expression and also reduced p53-induced apoptosis. Doxorubicin-induced apoptosis was also inhibited by Ipaf-directed small hairpin RNA. Our results show that p53 can directly induce Ipaf gene transcription, which contributes to p53-dependent apoptosis in at least some human cells.
机译：肿瘤抑制蛋白p53调节许多介导细胞周期停滞，凋亡，DNA修复和其他细胞反应的基因的转录。在这里，我们显示Ipaf是人CED-4的同源物，是caspase-1的激活剂，由p53诱导。在U2OS和A549细胞中转染p53的过表达增加了Ipaf mRNA水平。用DNA破坏药物阿霉素治疗p53阳性细胞系U2OS和MCF-7，阿霉素可提高p53蛋白水平，诱导Ipaf mRNA表达，但对MCF-7-mp53的处理类似（表达突变体的MCF-7细胞克隆p53）和p53阴性的K562细胞显示出的Ipaf基因表达诱导少得多。 Ipaf mRNA在阿霉素处理的人肿瘤细胞系中的表达分析表明，p53依赖性和p53依赖性机制以细胞类型特异性方式参与Ipaf基因表达的调节。 Ipaf启动子被正常的p53激活，但未被p53的His273突变体激活。在Ipaf启动子中鉴定了功能性p53结合位点。 Ipaf的显性负突变体抑制p53诱导的和阿霉素诱导的凋亡约50％。 Ipaf指导的小发夹RNA下调p53诱导的Ipaf基因表达，并减少p53诱导的细胞凋亡。 Ipaf定向的小发夹RNA也抑制了阿霉素诱导的细胞凋亡。我们的结果表明，p53可以直接诱导Ipaf基因转录，从而至少在某些人类细胞中促成p53依赖性细胞凋亡。

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